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A 24-Week Efficacy, Safety and Tolerability of Rivastigmine Patch Study in Patients With Probable Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Rivastigmine Patch
Rivastigmine Capsules
Placebo to Rivastigmine patch
Placebo to Rivastigmine capsules
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's, Rivastigmine, Patch, Dementia

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • have a diagnosis of dementia of the Alzheimer's type according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria;
  • have a clinical diagnosis of probable AD according to NINCDS/ADRDA criteria.
  • have a brain scan (magnetic resonance imaging (MRI) or computed tomography (CT)) consistent with the diagnosis of AD. The brain scan must have been performed within one year prior to randomization;
  • have an MMSE score of ≥ 10 and ≤ 20;
  • have sufficient education to have been able to read, write, and communicate effectively during the premorbid state;
  • be residing with someone in the community throughout the study or, if living alone, in contact with the primary caregiver everyday;

Exclusion criteria:

  • have an advanced, severe, progressive, or unstable infectious, metabolic, immune, endocrinologic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological condition that may interfere with efficacy and safety assessments or put the patient at special risk;
  • have a history or current diagnosis of any medical or neurological condition other than AD that is identified as contributing cause of the patient's dementia;
  • have a current diagnosis of probable or possible vascular dementia according to the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria (NINDS-AIREN);
  • have a score of > 4 on the Modified Hachinski Ischemic Scale (MHIS);
  • have a current DSM-IV diagnosis of major depression, unless, in the opinion of the investigator, is in remission for at least 12 weeks;

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Rivastigmine patch

Rivastigmine capsules

Arm Description

Once-daily target patch size 10 cm²

Twice-daily target dose of 6 mg oral capsule

Outcomes

Primary Outcome Measures

Change From Baseline on Cognition, Assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)
The Alzheimer's Disease Assessment Scale (ADAS) is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. It was assessed by a mental health professional (e.g., M.D., Ph.D., Pharm.D., R.N., or other equivalent qualifications) with a minimum of 2 years research experience meeting certification requirements.

Secondary Outcome Measures

Change From Baseline in Global Functioning, Assessed by the Alzheimer's Disease Assessment Scale Clinical Impression of Change (ADCS-CGIC)
Alzheimer's disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale provides a single global rating of change from baseline. It was recommended that the baseline interview be conducted by two raters, one designated as the primary rater, the other as a backup. Both raters were independent trained clinicians, experienced in the assessment of patients with dementia. Neither rater was involved in any other way with the patients' treatment or evaluation throughout the study. At baseline, both raters had access to all of the patient's available records and evaluations. Subsequently, for all ratings of change from baseline, the rater relied solely on information obtained during the baseline interview of the patient and caregiver, including written notes and, if available, the baseline interview audio- or videotape. The rater had no access to any other safety or efficacy data, including all previous post-baseline ADCS-CGIC ratings by either rater.
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score
Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is a caregiver-based Activities of Daily Living (ADL) scale composed of 23 items developed for use in dementia clinical studies. It was designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, as well as making judgments and decisions. Responses for each item were obtained from the caregiver through an interview. For each basic ADL, there was a forced choice of best response or a "yes" or "no" question with additional sub questions. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. Therefore, the higher total score, the higher functioning the patient was. The total score was the sum of all items and sub questions. The range for the total ADCS-ADL score was 0 to 78.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
NPI including Caregiver Distress Scale (NPI-D) assesses a wide range of behavior problems encountered in dementia patients to provide a means of distinguishing frequency and severity of changes in behavioral problems & facilitates rapid behavioral assessment using screening questions.10 behavioral problems & 2 neurovegetative domains were evaluated through an interview of the caregiver by a mental health professional. The scale includes both frequency & severity ratings of ea. domain as well as a composite domain score(frequency x severity). Frequency: 1(occasionally) - 4(very frequently)&severity:1(mild) - 3(marked).The sum of the composite scores of the 12 domains yields the NPI total score. The NPI-D: 0(not severe & not at all distressing) - 5 (very severe or extremely distressing) for each of the 12 domains. NPI-12 total score: from 0-144, the NPI-10 total score: from 0-120, & NPI-D score: from 0-60, all with higher scores indicating more severe behavioral disturbance.
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score
The Mini-Mental State Examination (MMSE) was used to establish patient's eligibility for the study and it was also used as an efficacy parameter in the Double-blind Treatment Period. The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score of 30, with higher scores indicating betterfunction. The total MMSE score at screening was between 10 and 20, inclusive, in order forthe patient to be eligible to participate in the trial.

Full Information

First Posted
July 19, 2011
Last Updated
July 10, 2014
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01399125
Brief Title
A 24-Week Efficacy, Safety and Tolerability of Rivastigmine Patch Study in Patients With Probable Alzheimer's Disease
Official Title
A 24-Week, Randomized, Double-blind, Double-dummy, Parallel-group, Active-controlled Study to Assess the Efficacy, Safety, and Tolerability of the Once-daily Rivastigmine Patch Formulation in Patients With Probable Alzheimer's Disease (Mini-Mental State Examination (MMSE) 10-20)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to assess the efficacy, safety, and tolerability of Exelon® patch in patients with probable AD (MMSE 10-20), in order to support a planned regulatory submission and registration of Exelon transdermal patch in China. The study is designed to confirm the non-inferiority of the efficacy of Exelon patch (target 10 cm² patch size) versus Exelon capsules (target 6.0 mg bid dose) on cognition, using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's, Rivastigmine, Patch, Dementia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
501 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rivastigmine patch
Arm Type
Experimental
Arm Description
Once-daily target patch size 10 cm²
Arm Title
Rivastigmine capsules
Arm Type
Active Comparator
Arm Description
Twice-daily target dose of 6 mg oral capsule
Intervention Type
Drug
Intervention Name(s)
Rivastigmine Patch
Other Intervention Name(s)
ENA713, Exelon
Intervention Description
Once-daily target patch size 10 cm²
Intervention Type
Drug
Intervention Name(s)
Rivastigmine Capsules
Other Intervention Name(s)
ENA713, Exelon
Intervention Description
Twice-daily target dose of 6 mg oral capsule
Intervention Type
Drug
Intervention Name(s)
Placebo to Rivastigmine patch
Other Intervention Name(s)
placebo
Intervention Description
Matching placebo to Rivastigmine patch
Intervention Type
Drug
Intervention Name(s)
Placebo to Rivastigmine capsules
Other Intervention Name(s)
placebo
Intervention Description
matching Placebo to Rivastigmine capsules
Primary Outcome Measure Information:
Title
Change From Baseline on Cognition, Assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)
Description
The Alzheimer's Disease Assessment Scale (ADAS) is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. It was assessed by a mental health professional (e.g., M.D., Ph.D., Pharm.D., R.N., or other equivalent qualifications) with a minimum of 2 years research experience meeting certification requirements.
Time Frame
Change at 24 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Global Functioning, Assessed by the Alzheimer's Disease Assessment Scale Clinical Impression of Change (ADCS-CGIC)
Description
Alzheimer's disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale provides a single global rating of change from baseline. It was recommended that the baseline interview be conducted by two raters, one designated as the primary rater, the other as a backup. Both raters were independent trained clinicians, experienced in the assessment of patients with dementia. Neither rater was involved in any other way with the patients' treatment or evaluation throughout the study. At baseline, both raters had access to all of the patient's available records and evaluations. Subsequently, for all ratings of change from baseline, the rater relied solely on information obtained during the baseline interview of the patient and caregiver, including written notes and, if available, the baseline interview audio- or videotape. The rater had no access to any other safety or efficacy data, including all previous post-baseline ADCS-CGIC ratings by either rater.
Time Frame
Change at 24 weeks
Title
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score
Description
Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) is a caregiver-based Activities of Daily Living (ADL) scale composed of 23 items developed for use in dementia clinical studies. It was designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, as well as making judgments and decisions. Responses for each item were obtained from the caregiver through an interview. For each basic ADL, there was a forced choice of best response or a "yes" or "no" question with additional sub questions. Higher numbered scores and answers of "yes" reflected a more self-sufficient individual. Therefore, the higher total score, the higher functioning the patient was. The total score was the sum of all items and sub questions. The range for the total ADCS-ADL score was 0 to 78.
Time Frame
Change at 24 weeks
Title
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score
Description
NPI including Caregiver Distress Scale (NPI-D) assesses a wide range of behavior problems encountered in dementia patients to provide a means of distinguishing frequency and severity of changes in behavioral problems & facilitates rapid behavioral assessment using screening questions.10 behavioral problems & 2 neurovegetative domains were evaluated through an interview of the caregiver by a mental health professional. The scale includes both frequency & severity ratings of ea. domain as well as a composite domain score(frequency x severity). Frequency: 1(occasionally) - 4(very frequently)&severity:1(mild) - 3(marked).The sum of the composite scores of the 12 domains yields the NPI total score. The NPI-D: 0(not severe & not at all distressing) - 5 (very severe or extremely distressing) for each of the 12 domains. NPI-12 total score: from 0-144, the NPI-10 total score: from 0-120, & NPI-D score: from 0-60, all with higher scores indicating more severe behavioral disturbance.
Time Frame
Change at 24 weeks
Title
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score
Description
The Mini-Mental State Examination (MMSE) was used to establish patient's eligibility for the study and it was also used as an efficacy parameter in the Double-blind Treatment Period. The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score of 30, with higher scores indicating betterfunction. The total MMSE score at screening was between 10 and 20, inclusive, in order forthe patient to be eligible to participate in the trial.
Time Frame
Change at 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: have a diagnosis of dementia of the Alzheimer's type according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria; have a clinical diagnosis of probable AD according to NINCDS/ADRDA criteria. have a brain scan (magnetic resonance imaging (MRI) or computed tomography (CT)) consistent with the diagnosis of AD. The brain scan must have been performed within one year prior to randomization; have an MMSE score of ≥ 10 and ≤ 20; have sufficient education to have been able to read, write, and communicate effectively during the premorbid state; be residing with someone in the community throughout the study or, if living alone, in contact with the primary caregiver everyday; Exclusion criteria: have an advanced, severe, progressive, or unstable infectious, metabolic, immune, endocrinologic, hepatic, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological condition that may interfere with efficacy and safety assessments or put the patient at special risk; have a history or current diagnosis of any medical or neurological condition other than AD that is identified as contributing cause of the patient's dementia; have a current diagnosis of probable or possible vascular dementia according to the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria (NINDS-AIREN); have a score of > 4 on the Modified Hachinski Ischemic Scale (MHIS); have a current DSM-IV diagnosis of major depression, unless, in the opinion of the investigator, is in remission for at least 12 weeks; Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Fuzhou
State/Province
Fujian
Country
China
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
Novartis Investigative Site
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215004
Country
China
Facility Name
Novartis Investigative Site
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China
Facility Name
Novartis Investigative Site
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100028
Country
China
Facility Name
Novartis Investigative Site
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200003
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200127
Country
China

12. IPD Sharing Statement

Learn more about this trial

A 24-Week Efficacy, Safety and Tolerability of Rivastigmine Patch Study in Patients With Probable Alzheimer's Disease

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